1. Field of the Invention (Technical Field)
The present invention relates to naphthalene-containing melanocortin receptor-specific small molecules, preferably specific for MC4-R, that are characterized in that they modulate feeding behavior in mammals without eliciting a sexual response, or significantly eliciting a sexual response, and methods for modulating feeding behavior in mammals without eliciting a sexual response, or significantly eliciting a response, by means of such MC4-R specific molecules.
2. Background Art
A family of melanocortin receptor types and subtypes have been identified, including melanocortin-1 receptors (MC1-R) expressed on normal human melanocytes and melanoma cells, melanocortin-2 receptors (MC2-R) for ACTH (adrenocorticotropin) expressed in cells of the adrenal gland, melanocortin-3 and melanocortin-4 receptors (MC3-R and MC4-R) expressed primarily in cells in the hypothalamus, mid-brain and brainstem, and melanocortin-5 receptors (MC5-R), expressed in a wide distribution of tissues.
Compounds specific for MC3-R or MC4-R, and particularly MC4-R, are believed to be useful in regulation of energy homeostasis, including use as agents for attenuating food intake and body weight gain, for use in treatment of anorexia, as a weight gain aid, for treatment of obesity, and other treatment of food intake and metabolism-related disorders and conditions. Compounds specific for MC3-R and/or MC4-R, and particularly MC4-R, affect sexual response, and can be used as agents for treatment of sexual dysfunction, including male erectile dysfunction.
Because of the myriad biological effects of compounds specific for melanocortin receptors, there is a need for methods, including selection of compounds, to differentiate the effects. More specifically, the MC4-R is commonly believed to be implicated in both energy homeostasis and sexual response. For most pharmaceutical applications it is desirably to have a compound that is specific for a single biological effect, such as for example an MC4-R agonist of high affinity that regulates energy homeostasis, such as by decreasing food intake and/or body weight, without inducing a sexual response.